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CRY2缺失通过增强PAX7表达和卫星细胞增殖来促进再生性肌生成。

Loss of CRY2 promotes regenerative myogenesis by enhancing PAX7 expression and satellite cell proliferation.

作者信息

Hao Yingxue, Xue Ting, Liu Song-Bai, Geng Sha, Shi Xinghong, Qian Panting, He Wei, Zheng Jiqing, Li Yanfang, Lou Jing, Shi Tianze, Wang Ge, Wang Xiaoxiao, Wang Yanli, Li Yangxin, Song Yao-Hua

机构信息

Cyrus Tang Hematology Center Collaborative Innovation Center of Hematology Soochow University Suzhou P. R. China.

National Clinical Research Center for Hematologic Diseases The First Affiliated Hospital of Soochow University Suzhou P. R. China.

出版信息

MedComm (2020). 2023 Jan 9;4(1):e202. doi: 10.1002/mco2.202. eCollection 2023 Feb.

DOI:10.1002/mco2.202
PMID:36636367
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9830134/
Abstract

The regenerative capacity of skeletal muscle is dependent on satellite cells. The circadian clock regulates the maintenance and function of satellite cells. Cryptochrome 2 (CRY2) is a critical component of the circadian clock, and its role in skeletal muscle regeneration remains controversial. Using the skeletal muscle lineage and satellite cell-specific CRY2 knockout mice (CRY2), we show that the deletion of CRY2 enhances muscle regeneration. Single myofiber analysis revealed that deletion of CRY2 stimulates the proliferation of myoblasts. The differentiation potential of myoblasts was enhanced by the loss of CRY2 evidenced by increased expression of myosin heavy chain (MyHC) and myotube formation in cells versus cells. Immunostaining revealed that the number of mononucleated paired box protein 7 (PAX7) cells associated with myotubes formed by cells was increased compared with cells, suggesting that more reserve cells were produced in the absence of CRY2. Loss of CRY2 leads to the activation of the ERK1/2 signaling pathway and ETS1, which binds to the promoter of PAX7 to induce its transcription. CRY2 deficient myoblasts survived better in ischemic muscle. Therefore, CRY2 is essential in regulating skeletal muscle repair.

摘要

骨骼肌的再生能力依赖于卫星细胞。生物钟调节卫星细胞的维持和功能。隐花色素2（CRY2）是生物钟的关键组成部分，其在骨骼肌再生中的作用仍存在争议。利用骨骼肌谱系和卫星细胞特异性CRY2基因敲除小鼠（CRY2-/-），我们发现CRY2的缺失增强了肌肉再生。单根肌纤维分析显示，CRY2的缺失刺激了成肌细胞的增殖。成肌细胞的分化潜能因CRY2的缺失而增强，这在与CRY2+/+细胞相比的CRY2-/-细胞中，肌球蛋白重链（MyHC）表达增加和肌管形成得到证实。免疫染色显示，与CRY2+/+细胞相比，CRY2-/-细胞形成的肌管相关的单核配对盒蛋白7（PAX7）细胞数量增加，这表明在CRY2缺失的情况下产生了更多的储备细胞。CRY2的缺失导致ERK1/2信号通路和ETS1的激活，ETS1与PAX7的启动子结合以诱导其转录。CRY2缺陷的成肌细胞在缺血肌肉中存活得更好。因此，CRY2在调节骨骼肌修复中至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d184/9830134/28b88169b9db/MCO2-4-e202-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d184/9830134/28b88169b9db/MCO2-4-e202-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d184/9830134/3e1989e40350/MCO2-4-e202-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d184/9830134/2910e900e7be/MCO2-4-e202-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d184/9830134/2ef6bd0f2c78/MCO2-4-e202-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d184/9830134/674beef38a06/MCO2-4-e202-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d184/9830134/99c2bea5dc50/MCO2-4-e202-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d184/9830134/28b88169b9db/MCO2-4-e202-g004.jpg

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